"Nature" New tRNA-based inhibitory gene therapy

According to a new paper published in the journal Nature, gene therapy researchers at the University of Massachusetts Medical School have demonstrated for the first time that in a rare mouse model of mucopolysaccharidosis type I, inhibitory transfer RNA (tRNA) therapy can Protein production was restored after 6 months of treatment

Dr.

Gene replacement and transgenic therapy focus on repairing or rebuilding defective genetic material to produce a therapeutic effect

"Our study is the first to provide evidence in an animal model of human disease that tRNA-based therapy can safely restore gene expression," said Wang, PhD, assistant professor of RNA therapeutics

Transfer RNAs play a key role in the formation of intracellular proteins

In every mRNA instruction sheet there is an additional instruction called a stop codon that tells the ribosomal machinery when the protein is done and when to stop adding amino acids

"About 11 percent of genetic diseases are caused by single-nucleotide mutations that cause premature stop codons," explains co-author Dr.

Wang and Gao developed an inhibitory tRNA that allows the ribosomal machinery to skip these premature stop codons, allowing the protein-making machinery to continue building a fully functional protein

Mutations in the IDUA gene cause lysosomal storage disorders in mucopolysaccharidosis type

Gao and Wang chose to test their AAV NoSTOP on mucopolysaccharidosis type I because the biochemical effects of the disease are present throughout the body, allowing the study of multiple tissue types

Although tRNA technology has been around for more than 40 years, the inability to assess the biochemical impact of modifying tRNA sequences has slowed the translation of the technology into therapeutics

The findings support the idea that inhibiting tRNA can restore normal protein production

"When combined with AAV-based gene delivery technologies developed for different tissues, the AAV NoSTOP platform will be a potentially valuable clinical complement for developing gene-based therapies," said Gao

Courtesy of the University of Massachusetts Medical School